HIV integrase. We have been engaged in a structural analysis of the HIV integrase, and have previously reported the crystallization and structure determination of the catalytic core domain, residues 50-212. We have crystallized this core domain in several different crystal forms. Analysis of these crystals reveals more details about some of the residues that were disordered in the original structure. Crystals prepared in the presence of Mg++, a known cofactor, now show clear evidence for the binding of this cation at the active site of the enzyme. We have also prepared a variety of other fragments of the integrase in an effort to crystallize the core domain coupled to either or both of the remaining domains. We have been able to bind an inhibitor to the active site of the enzyme. This inhibitor binds centrally in the site and provides a new lead compound for antiviral drug design. Crystals have been examined with other inhibitors. A new crystal form has been discovered.